Abstract and Introduction
Cushing disease is considered an aggressive pituitary endocrinopathy because of the devastating effects from untreated hypercortisolemia. Although they are histologically benign, these adrenocorticotropic hormone (ACTH)-secreting pituitary tumors are associated with significant morbidity and premature death. Currently, transsphenoidal surgery is the primary treatment of Cushing disease associated with an ACTH-secreting pituitary tumor, resulting in remission rates ranging from about 50 to 90%.
Some patients, however, will not achieve sustained remission after transsphenoidal surgery and can exhibit persistent or recurrent Cushing disease that requires multimodal treatment to achieve remission. In these patients, options for treatment include repeat transsphenoidal resection, radiation therapy (including conventional fractionated radiation therapy and stereotactic radiosurgery), and medical therapy. Despite undergoing multiple treatment modalities, some patients may ultimately require bilateral adrenalectomy for definitive treatment to eliminate hypercortisolemia associated with Cushing disease. In this article, the authors review the treatment options for patients who have persistent or recurrent Cushing disease after unsuccessful transsphenoidal surgery. The indications, current results reported in the literature, and complications of each treatment modality are discussed.
Cushing disease, which is induced by a functional ACTH-producing adenoma of the anterior pituitary gland, is the most common cause of ACTH-dependent Cushing syndrome. The treatment of Cushing disease remains challenging for neurosurgeons and endocrinologists. Transsphenoidal surgery is currently the treatment of choice in patients who harbor ACTH-secreting pituitary tumors associated with Cushing disease. This surgery provides the best option for rapid biochemical remission with excellent long-term results. Remission rates after transsphenoidal resection performed by experienced surgeons have ranged from approximately 70 to 90%.[3,9,15,17,26,37,38,42,47,54] Long-term follow-up with biochemical testing is necessary to detect tumor recurrence because remission rates decline with longer follow-up periods.[14,16] Although many patients achieve complete remission, these tumors are difficult to cure surgically, and some patients may exhibit persistent or recurrent hypersecretion of ACTH and hypercortisolism resulting in increased morbidity and death related to their malignant endocrinopathy. Unfortunately, the results of endocrinological analyses after transsphenoidal surgery vary in the literature because different definitions of a biochemical cure are given in the various studies.
If biochemical evidence of Cushing disease persists or recurs after an initial transsphenoidal surgery, the surgeon should be familiar with the treatment options available to offer the patient, including repeat transsphenoidal surgery, radiation therapy, medical therapy, and bilateral adrenalectomy. A multimodal approach using a combination of these treatments may be an appropriate strategy in some patients to achieve the best outcome. For optimal results, a multidisciplinary team approach should be coordinated at a specialized center. In this paper, we provide an overview of the management options available after unsuccessful transsphenoidal surgery and review the current outcome data for each option based on results reported in the literature.
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